The analgesic effects of morphine, but not those of the enkephalinase inhibitor thiorphan, are enhanced in arthritic rats

Abstract

The effects of various i.v. doses of morphine (0.1, 0.3 and 1 mg/kg) and of thiorphan, an inhibitor of enkephalinase (0.7, 2.5, 5, 10 and 15 mg/kg), were studied upon the vocalization threshold to foot pressure in normal rats and rats with Freund's adjuvant-induced arthritis. The vocalization threshold in arthritic rats was, before any injections, significantly lower than in normal rats (mean pressure threshold for vocalization: 115.2 g +/- 14.7 (n = 152) for arthritic rats vs 182.5 g +/- 21.3 for normal rats (n = 152). The various doses of morphine in raising the vocalization threshold were more efficient in arthritic than in normal rats (maximum vocalization threshold (% of control) following 1 mg/kg morphine = 225.70 +/- 10.21 in arthritic rats vs 140.75 +/- 6.87 in normal rats, n = 9 in each case). This effect was dose-dependent, and in every case, naloxone-reversible. Injected at doses of 5-15 mg/kg, thiorphan increased the vocalization threshold (maximum = 223.91% +/- 11.96 in arthritic rats vs 223.30% +/- 5.93 in normal rats for 15 mg/kg i.v., n = 9 for each group). This effect was not greater in arthritic than in normal rats. The dose of 2.5 mg/kg of thiorphan was insufficient. Administered at 0.7 mg/kg, thiorphan significantly decreased the vocalization threshold in the arthritic rats only. These effects of thiorphan were all naloxone-reversible using doses of naloxone which were one-hundredth of those of thiorphan.